tbuckley/cabot-search huggingface dataset:
CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models
Authors: Joyce Wei, Welby Montalvo-Ortiz, Lola Yu, Amanda Krasco, Kara Olson, Sahar Rizvi, Nathalie Fiaschi, Sandra Coetzee, Fang Wang, Erica Ullman, Hassan Shakil Ahmed, Evan Herlihy, Ken Lee, Lauren Havel, Terra Potocky, Sarah Ebstein, Davor Frleta, Aditi Khatri, Stephen Godin, Sara Hamon, Jurriaan Brouwer-Visser, Travis Gorenc, Doug MacDonald, Aynur Hermann, Aafia Chaudhry, Andres Sirulnik, William Olson, John Lin, Gavin Thurston, Israel Lowy, Andrew J. Murphy, Eric Smith, Vladimir Jankovic, Matthew A. Sleeman, Dimitris Skokos
Journal: Science Translational Medicine (2022)

Although many patients with diffuse large B cell lymphoma (DLBCL) may achieve a complete response to frontline chemoimmunotherapy, patients with relapsed/refractory disease typically have poor outcomes. Odronextamab, a CD20xCD3 bispecific antibody that provides “signal 1” through the activation of the T cell receptor/CD3 complex, has exhibited early, promising activity for patients with highly refractory DLBCL in phase 1 trials. However, not all patients achieve complete responses, and many relapse, thus representing a high unmet medical need. Here, we investigated whether adding a costimulatory “signal 2” by engaging CD28 receptors on T cells could augment odronextamab activity. We demonstrate that REGN5837, a bispecific antibody that cross-links CD22-expressing tumor cells with CD28-expressing T cells, enhances odronextamab by potentiating T cell activation and cytolytic function. In preclinical DLBCL studies using human immune system–reconstituted animals, REGN5837 promotes the antitumor activity of odronextamab and induces intratumoral expansion of reprogrammable T cells while skewing away from a dysfunctional state. Although REGN5837 monotherapy shows limited activity and no toxicity in primate studies, it augments T cell activation when dosed in combination with odronextamab. In addition, analysis of non-Hodgkin lymphoma clinical samples reveals an increase in CD28 + CD8 + T cells after odronextamab treatment, demonstrating the presence of a population that could potentially be targeted by REGN5837. Collectively, our data demonstrate that REGN5837 can markedly enhance the antitumor activity of odronextamab in preclinical NHL models, and the combination of these two bispecific antibodies may provide a chemotherapy-free approach for the treatment of DLBCL.
Genetic Ancestry Inference from Cancer-Derived Molecular Data across Genomic and Transcriptomic Platforms
Authors: Pascal Belleau, Astrid Deschênes, Nyasha Chambwe, David A. Tuveson, Alexander Krasnitz
Journal: Cancer Research (2022)

Abstract Genetic ancestry–oriented cancer research requires the ability to perform accurate and robust genetic ancestry inference from existing cancer-derived data, including whole-exome sequencing, transcriptome sequencing, and targeted gene panels, very often in the absence of matching cancer-free genomic data. Here we examined the feasibility and accuracy of computational inference of genetic ancestry relying exclusively on cancer-derived data. A data synthesis framework was developed to optimize and assess the performance of the ancestry inference for any given input cancer-derived molecular profile. In its core procedure, the ancestral background of the profiled patient is replaced with one of any number of individuals with known ancestry. The data synthesis framework is applicable to multiple profiling platforms, making it possible to assess the performance of inference specifically for a given molecular profile and separately for each continental-level ancestry; this ability extends to all ancestries, including those without statistically sufficient representation in the existing cancer data. The inference procedure was demonstrated to be accurate and robust in a wide range of sequencing depths. Testing of the approach in four representative cancer types and across three molecular profiling modalities showed that continental-level ancestry of patients can be inferred with high accuracy, as quantified by its agreement with the gold standard of deriving ancestry from matching cancer-free molecular data. This study demonstrates that vast amounts of existing cancer-derived molecular data are potentially amenable to ancestry-oriented studies of the disease without requiring matching cancer-free genomes or patient self-reported ancestry. Significance: The development of a computational approach that enables accurate and robust ancestry inference from cancer-derived molecular profiles without matching cancer-free data provides a valuable methodology for genetic ancestry–oriented cancer research.
Health-code-based triage versus universal COVID-19 PCR testing before endoscopy in a low incidence area: a real-world experience
Authors: Zhihui Duan, Dengxiang Liu, Shengyun Zhou, Hui Li, Xiaofang Sun, Chunqian Zhao, Qiong Duan, Liwei Li, Xiaochong Zhang, Lingxuan Jin
Journal: Gut (2022)
Promoting oral mucosal wound healing using a DCS-RuB2A2 hydrogel based on a photoreactive antibacterial and sustained release of BMSCs
Authors: Wenxin Qi, Naijun Dong, Lingling Wu, Xueqi Zhang, He Li, Hao Wu, Natalie Ward, Jian Yu, He Liu, Jiao Wang, Xiaoyong Deng, Robert Chunhua Zhao
Journal: Bioactive Materials (2022)

The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB2A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB2A2-BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.
Engineering white blood cell membrane-camouflaged nanocarriers for inflammation-related therapeutics
Authors: Wanli Song, Pengfei Jia, Yaping Ren, Junmiao Xue, Bingqian Zhou, Xinkai Xu, Yansheng Shan, Jing Deng, Qihui Zhou
Journal: Bioactive Materials (2022)

White blood cells (WBCs) play essential roles against inflammatory disorders, bacterial infections, and cancers. Inspired by nature, WBC membrane-camouflaged nanocarriers (WBC-NCs) have been developed to mimic the "dynamic" functions of WBCs, such as transendothelial migration, adhesion to injured blood vessels, etc, which make them promising for diverse medical applications. WBC-NCs inherit the cell membrane antigens of WBCs, while still exhibiting the robust inflammation-related therapeutic potential of synthetic nanocarriers with excellent (bio)physicochemical performance. This review summarizes the proposed concept of cell membrane engineering, which utilizes physical engineering, chemical modification, and biological functionalization technologies to endow the natural cell membrane with abundant functionalities. In addition, it highlights the recent progress and applications of WBC-NCs for inflammation targeting, biological neutralization, and immune modulation. Finally, the challenges and opportunities in realizing the full potential of WBC-NCs for the manipulation of inflammation-related therapeutics are discussed.
Spontaneous immunomodulation and regulation of angiogenesis and osteogenesis by Sr/Cu-borosilicate glass (BSG) bone cement to repair critical bone defects
Authors: Shuaijie Li, Liyan Zhang, Chunyu Liu, Jua Kim, Kun Su, Tingli Chen, Limin Zhao, Xiaomei Lu, Hao Zhang, Yinglin Cui, Xu Cui, Feng Yuan, Haobo Pan
Journal: Bioactive Materials (2022)

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing. In vitro studies showed that the controlled release of Sr and Cu ions up-regulated anti-inflammatory genes(IL-1Ra and TGF-β1) while down-regulating pro-inflammatory genes(IL-1β and IL-6) in macrophages at 3 days. Sr and Cu ions also increased the expressions of angiogenic genes (VEGF and bFGF) in HUVECs at 5 days and osteogenic genes (Runx-2, OCN, and OPN) in hBMSCs at 7, 14, and 21 days. 5Sr3Cu-BSG bone cement exhibited the best anti-inflammatory, angiogenic, and osteogenic properties among the bone cement groups with different Sr and Cu ratios. Short-term and long-term implantation of Sr/Cu-BSGs in femoral condylar bone defects of rats and rabbits confirmed the in vitro results, where the degradation rate of Sr/Cu-BSG matched the bone healing rate. Similar to in vitro, the 5Sr3Cu-BSG group also showed the highest bone formation in vivo. Excellent physical and chemical properties, along with its bone repairing ability, make the Sr/Cu-BSG bone cement a good candidate biomaterial for treating bone defects.
Tuft Cells: Context- and Tissue-Specific Programming for a Conserved Cell Lineage
Authors: Maya E. Kotas, Claire E. O'Leary, Richard M. Locksley
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

Tuft cells are found in tissues with distinct stem cell compartments, tissue architecture, and luminal exposures but converge on a shared transcriptional program, including expression of taste transduction signaling pathways. Here, we summarize seminal and recent findings on tuft cells, focusing on major categories of function—instigation of type 2 cytokine responses, orchestration of antimicrobial responses, and emerging roles in tissue repair—and describe tuft cell–derived molecules used to affect these functional programs. We review what is known about the development of tuft cells from epithelial progenitors under homeostatic conditions and during disease. Finally, we discuss evidence that immature, or nascent, tuft cells with potential for diverse functions are driven toward dominant effector programs by tissue- or perturbation-specific contextual cues, which may result in heterogeneous mature tuft cell phenotypes both within and between tissues.
The Development and Consequences of Red Blood Cell Alloimmunization
Authors: Connie M. Arthur, Sean R. Stowell
Journal: Annual Review of Pathology Mechanisms of Disease (2022)

While red blood cell (RBC) transfusion is the most common medical intervention in hospitalized patients, as with any therapeutic, it is not without risk. Allogeneic RBC exposure can result in recipient alloimmunization, which can limit the availability of compatible RBCs for future transfusions and increase the risk of transfusion complications. Despite these challenges and the discovery of RBC alloantigens more than a century ago, relatively little has historically been known regarding the immune factors that regulate RBC alloantibody formation. Through recent epidemiological approaches, in vitro–based translational studies, and newly developed preclinical models, the processes that govern RBC alloimmunization have emerged as more complex and intriguing than previously appreciated. Although common alloimmunization mechanisms exist, distinct immune pathways can be engaged, depending on the target alloantigen involved. Despite this complexity, key themes are beginning to emerge that may provide promising approaches to not only actively prevent but also possibly alleviate the most severe complications of RBC alloimmunization.
Optimizing referral practices for resection of large colorectal polyps
Authors: Jennifer M. Kolb
Journal: Endoscopy (2022)

There has been an increasing focus on educating and encouraging referral of large complex colorectal polyps to an advanced endoscopist for endoscopic mucosal resection (EMR) or submucosal dissection (ESD) and on discouraging physicians from sending these patients for unnecessary surgery. However, practice patterns vary widely depending on the available resources, training, and preferences of the referring and accepting physician. Endoscopists who may not be comfortable removing large polyps or lack the equipment for these procedures will often take a biopsy on the initial examination to 1) rule out cancer, 2) provide results and reassurance to the patient, and 3) include pathology in the referral. We frequently hear frustration from endoscopists on the receiving end that these biopsies cause submucosal fibrosis and make the resection more challenging. However much of this is anecdotal, with few data to support these complaints. Finally, we have more insight into the value and detriment of biopsy prior to EMR.
18F-FDG PET/CT of Primary Extraskeletal Ewing Sarcoma of the Prostate
Authors: Yue-Hong Guo, Min-Fu Yang
Journal: Clinical Nuclear Medicine (2022)

Abstract Prostate Ewing sarcoma is rare. We report the 18 F-FDG PET/CT finding of a 16-year-old adolescent boy who presented with dysuria and was confirmed to be extraskeletal Ewing sarcoma of the prostate by histopathologic findings.
Laparoscopic Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass in Adult Patients With Obesity—Reply
Authors: Paulina Salminen, Sofia Grönroos, Mika Helmiö
Journal: JAMA Surgery (2022)

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Therapeutic Efficacy and Prediction of 18F-FDG PET/CT-Assisted Botulinum Toxin Therapy in Patients With Idiopathic Cervical Dystonia
Authors: Hye Ryeong Kwon, Hyunjong Lee, Duk Hyun Sung, Joon Young Choi
Journal: Clinical Nuclear Medicine (2022)

Purpose This study aimed to investigate the therapeutic efficacy of 18 F-FDG PET/CT-assisted botulinum toxin (BTX) injection therapy and predictive PET findings in relation to a good response in patients with idiopathic cervical dystonia (ICD). Materials and Methods A total of 78 patients was enrolled from November 2007 to July 2018. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score was determined at baseline and 4 weeks after BTX injection guided by electromyography and PET/CT. The number of hypermetabolic muscles, the highest SUV max among hypermetabolic muscles, and the total SUV max of hypermetabolic muscles were evaluated as pretreatment PET parameters. A good response was defined as a reduction rate ≥30% and a point decrease ≥15 of the TWSTRS total score. Results Half of the subjects showed a good response. Good responders had significantly higher baseline TWSTRS scores than poor responders (total score, P &lt; 0.001; severity, P &lt; 0.001; disability, P &lt; 0.001; pain, P = 0.026). Good responders also had significantly higher numbers of hypermetabolic muscles and BTX-injected hypermetabolic muscles ( P &lt; 0.001, both). In multivariable analysis, the baseline TWSTRS disability subscale score and the number of BTX-injected hypermetabolic muscles were significant predictors for good response ( P = 0.001 and P = 0.028). The aforementioned 3 PET parameters were positively correlated with the baseline TWSTRS scores. In addition, PET/CT well detected dystonic deep cervical muscles. Conclusions FDG PET/CT-assisted BTX injection therapy showed good therapeutic efficacy in ICD patients. The numbers of hypermetabolic cervical muscles and BTX-injected hypermetabolic muscles may be helpful in predicting a good response.
Double-Blind, Sham-Controlled Randomized Trial Testing the Efficacy of fMRI Neurofeedback on Clinical and Cognitive Measures in Children With ADHD
Authors: Sheut-Ling Lam, Marion Criaud, Steve Lukito, Samuel J. Westwood, Deborah Agbedjro, Olivia S. Kowalczyk, Sarah Curran, Nadia Barret, Chris Abbott, Holan Liang, Emily Simonoff, Gareth J. Barker, Vincent Giampietro, Katya Rubia
Journal: American Journal of Psychiatry (2022)

Objective: Functional MRI neurofeedback (fMRI-NF) could potentially be a novel, safe nonpharmacological treatment for attention deficit hyperactivity disorder (ADHD). A proof-of-concept randomized controlled trial of fMRI-NF of the right inferior frontal cortex (rIFC), compared to an active control condition, showed promising improvement of ADHD symptoms (albeit in both groups) and in brain function. However, comparison with a placebo condition in a larger trial is required to test efficacy. Methods: This double-blind, sham-controlled randomized controlled trial tested the effectiveness and efficacy of fMRI-NF of the rIFC on symptoms and executive functions in 88 boys with ADHD (44 each in the active and sham arms). To investigate treatment-related changes, groups were compared at the posttreatment and 6-month follow-up assessments, controlling for baseline scores, age, and medication status. The primary outcome measure was posttreatment score on the ADHD Rating Scale (ADHD-RS). Results: No significant group differences were found on the ADHD-RS. Both groups showed similar decreases in other clinical and cognitive measures, except for a significantly greater decrease in irritability and improvement in motor inhibition in sham relative to active fMRI-NF at the posttreatment assessment, covarying for baseline. There were no significant side effects or adverse events. The active relative to the sham fMRI-NF group showed enhanced activation in rIFC and other frontal and temporo-occipital-cerebellar self-regulation areas. However, there was no progressive rIFC upregulation, correlation with ADHD-RS scores, or transfer of learning. Conclusions: Contrary to the hypothesis, the study findings do not suggest that fMRI-NF of the rIFC is effective in improving clinical symptoms or cognition in boys with ADHD.
Predictors of anemia response to momelotinib therapy in myelofibrosis and impact on survival
Authors: Naseema Gangat, Kebede H. Begna, Aref Al‐Kali, William Hogan, Mark Litzow, Animesh Pardanani, Ayalew Tefferi
Journal: American Journal of Hematology (2022)

We retrospectively reviewed 72 anemic patients with myelofibrosis (MF; median age 68 years), who were JAK2 inhibitor-naïve at the time of study entry to a phase-1/2 momelotinib clinical trial. Driver mutation profile included JAK2 69%, CALR 17%, MPL 8%, and triple-negative 6%; other mutations included ASXL1 39% and SRSF2 17%. Momelotinib was administered at a median dose of 300 mg daily. Anemia response was assessed by formal criteria and documented in 44% of all patients with hemoglobin levels below the sex-adjusted reference range (n = 72), 48% of those with hemoglobin <10 g/dl (n = 54), and 46% of those who were transfusion-dependent at the time of study entry (n = 28). Anemia response was more likely with post-essential thrombocythemia MF (83% vs 37%; p = .001), lower serum ferritin (p = .003), and shorter time from diagnosis to momelotinib therapy (p = .001); the first two variables were also predictive in transfusion-dependent patients. Post-momelotinib median survival was 3.2 years; in univariate analysis, survival was superior in anemia responders (median 3.8 vs. 2.8 years; p = .14) and in the presence of type 1/like CALR mutation and inferior in the presence of age > 65 years, ASXL1/SRSF2 mutation, unfavorable karyotype, DIPSS-plus high risk, red cell transfusion need and higher serum ferritin. Multivariable analysis confirmed the favorable impact of anemia response on survival (p = .02; HR 0.5, 3/5/10-year survival; 69%/38%/25%). This survival advantage was also noted in transfusion-dependent patients (3.7 vs. 1.9 years; p = .01; HR 0.3) and appeared to be restricted to patients with an unfavorable genetic profile. The current study suggests a short-term survival benefit associated with anemia response in momelotinib-treated patients with MF.
The 99mTc-MIP-1404 PSMA Uptake in the Isolated Paratracheal Lymph Node From the Prostate Adenocarcinoma
Authors: Justinas Jonusas, Sigitas Tiskevicius, Ernestas Janulionis
Journal: Clinical Nuclear Medicine (2022)

Abstract The oncologist consulted a 56-year-old man after receiving prostate-specific antigen screening results. Prostate-specific antigen level during the screen time was 33 ng/mL. As a result, poorly differentiated prostate adenocarcinoma with a Gleason score of 9 (5 + 4) was diagnosed. SPECT/CT scan with 99m Tc-MIP-1404 PSMA tracer was performed. The 99m Tc-PSMA–positive lesions were detected in the prostate, external iliac, obturator lymph nodes of the pelvis, para-aortic, and the right lower paratracheal space. The patient was prescribed androgen deprivation therapy and early chemotherapy with docetaxel (6 fractions), after which radiation therapy to prostate and seminal vesicles was planned.